The present invention relates to spectrometry, and more particularly, to methodology and apparatus for the analysis of compounds by chromatography-high field asymmetric waveform ion mobility spectrometry.
There is a developing interest in making in situ measurements of chemicals present in complex mixtures at industrial or environmental venues. A fully functional chemical sensor system may incorporate a front end, e.g., a gas chromatography (GC) analyzer as a compound separator, and then a detector, i.e., a spectrometer.
Gas chromatography is a chemical compound separation method in which a discrete gas sample (composed of a mixture of chemical components) is introduced via a shutter arrangement into a GC column. Components of the introduced gas sample are partitioned between two phases: one phase is a stationary bed with a large surface area, and the other is a gas which percolates through the stationary bed. The sample is vaporized and carried by the mobile gas phase (the carrier gas) through the column. Samples partition (equilibrate) into the stationary (liquid) phase, based on their solubilities into the column coating at the given temperature. The components of the sample separate from one another based on their relative vapor pressures and affinities for the stationary bed, this process is called elution.
The heart of the chromatograph is the column; the first ones were metal tubes packed with inert supports on which stationary liquids were coated. Presently, the most popular columns are made of fused silica and are open tubes with capillary dimensions. The stationary liquid phase is coated on the inside surface of the capillary wall.
Compounds are discriminated by the time that they are retained in the GC column (the time from sample injection to the time the peak maximum appears). Chemical species are identified from a sample based on their retention time. The height of any one of these peaks indicates the intensity or concentration of the specific detected compound.
A carrier gas (e.g., helium, filtered air, nitrogen) flows continuously through the injection port, and the column. The flow rate of the carrier gas must be carefully controlled to ensure reproducible retention times and to minimize detector drift and noise. The sample is usually injected (often with a microsyringe) into a heated injection port where it is vaporized and carried into the column, often capillary columns 15 to 30 meters long are used but for fast GC they can be significantly shorter (less than 1 meter), coated on the inside with a thin (e.g., 0.2 micron) film of high boiling liquid (the stationary phase). The sample partitions between the mobile and stationary phases, and is separated into individual components based on relative solubility in the liquid phase and relative vapor pressures. After the column, the carrier gas and sample pass through a detector that typically measures the quantity of the sample, and produces an electrical signal representative thereof.
Certain components of high speed or portable GC analyzers have reached advanced stages of refinement. These include improved columns and injectors, and heaters that achieve precise temperature control of the column. Even so, detectors for portable gas chromatographs still suffer from relatively poor detection limits and sensitivity. In addition, GC analyzers combined with any of the conventional detectors—flame ionization detectors (FID), thermal conductivity detectors, or photo-ionization detectors—simply produce a signal indicating the presence of a compound eluted from the GC column. However, presence indication alone is often inadequate, and it is often desirable to obtain additional specific information that can enable unambiguous compound identification.
One approach to unambiguous compound identification employs a combination of instruments capable of providing an orthogonal set of information for each chromatographic peak. (The term orthogonal will be appreciated by those skilled in the art to mean data which enables multiple levels of reliable and accurate identification of a particular species, and uses a different property of the compound for identification.) One such combination of instruments is a GC attached to a mass spectrometer (MS). The mass spectrometer is generally considered one of the most definitive detectors for compound identification, as it generates a fingerprint pattern of fragment ions for each compound eluting from the GC. Use of the mass spectrometer as the detector dramatically increases the value of analytical separation provided by the GC. The combined GC-MS information, in most cases, is sufficient for unambiguous identification of the compound.
Unfortunately, the GC-MS is not well suited for small, low cost, fieldable instruments. Therefore there is still a strong need to be met with a fieldable chemical sensor that can generate reliable orthogonal information. A successful field instrument should include both a small injector/column and a small detector/spectrometer and yet be able to rapidly produce unambiguous orthogonal data for identification of a detected compound.
While GC's are continuously being miniaturized and reduced in cost, mass spectrometers are still very expensive, easily exceeding $100K. Their size remains relatively large, making them difficult to deploy in the field. Mass spectrometers also suffer from the need to operate at low pressures, and their spectra can be difficult to interpret often requiring a highly trained operator. The search therefore has continued for fieldable spectrometer.
Time-of-flight Ion Mobility Spectrometers (TOF-IMS) have been described as detectors for gas chromatographs from early in the development of ion mobility spectrometry and the first successful use of TOF-IMS detectors with capillary chromatography occurred in 1982. High-speed response and low memory effects were attained and the gas phase ion chemistry inside the TOF-IMS can be highly reproducible providing the foundation to glean chemical class information from mobility spectra. Thus, TOF-IMS, as ionization detectors for GC, do exhibit functional parallels to mass spectrometers, except all processes in IMS occur at ambient pressure making vacuum systems unnecessary. The IMS spectra is also simpler to interpret since it contains fewer peaks, due to less ion fragmentation. The usefulness of a gas chromatograph with TOF-IMS detector has been recognized for air quality monitoring, chemical agent monitoring, explosives detection, and for some environmental uses.
Fieldability still remains a problem for TOF-IMS. Despite advances over the past decade, TOF-IMS drift tubes are still comparatively large and expensive and suffer from losses in detection limits when made small. The search therefore still continues for a successful field instrument that includes both a small ion injector/column and a small detector/spectrometer and yet is able to rapidly produce unambiguous orthogonal data for identification of a detected compound.
The high field asymmetric waveform ion mobility spectrometer (FAIMS) is an alternative to the TOF-IMS. In a FAIMS device, a gas sample that contains a chemical compound is subjected to an ionization source. Ions from the ionized gas sample are drawn into an ion filter and subjected to a high field asymmetric waveform ion mobility filtering technique. Select ion species allowed through the filter are then passed to an ion detector, enabling indication of a selected species.
The FAIMS filtering technique involves passing ions in a carrier gas through strong electric fields between the filter electrodes. The fields are created by application of an asymmetric period voltage (typically along with a further control bias) to the filter electrodes.
The process achieves a filtering effect by accentuating differences in ion mobility. The asymmetric field alternates between a high and low field strength condition that causes the ions to move in response to the field according to their mobility. Typically the mobility in the high field differs from that of the low field. That mobility difference produces a net displacement of the ions as they travel in the gas flow through the filter. In absence of a compensating bias signal, the ions will hit one of the filter electrodes and will be neutralized. In the presence of a specific bias signal, a particular ion species will be returned toward the center of the flow path and will pass through the filter. The amount of change in mobility in response to the asymmetric field is compound-dependent. This permits separation of ions from each other according to their species, in the presence of an appropriately set bias.
In the past, Mine Safety Appliances Co. (MSA) made an attempt at a functional FAIMS implementation in a cylindrical device, such as disclosed in U.S. Pat. No. 5,420,424. (It is referred to by MSA as a Field Ion Spectrometer (FIS), see FIG. 1.) The device is complex, with many parts, and is somewhat limited in utility.
Fast detection is a sought-after feature of a fieldable detection device. One characteristic of known FAIMS devices is the relatively slow detection time. However, the GC operates much more rapidly, such that the known FAIMS devices cannot generate a complete spectra of the ions present under each GC peak. Therefore these FAIMS devices would have to be limited to a single compound detection mode if coupled to a GC, with a response time of about 10 seconds. Any additional compound that is desired to be measured will take approximately an additional 10 seconds to measure.
While the foregoing arrangements are adequate for a number of applications, it is still desirable to have a small, fieldable ion detector/spectrometer that can render real-time or near real-time indications of detected chemical compounds, such as for use on a battlefield and in other environments.
Furthermore, a GC-FAIMS arrangement, focused as it is on one species at a time, is incapable of simultaneous detection of a broad range of species, such as would be useful for airport security detectors, or on a battlefield, or in industrial environments. Such equipment is also incapable of simultaneous detection of both positive and negative ions in a gas sample.
It is therefore an object of the present invention to provide a functional, small, fieldable ion detector/spectrometer that overcomes the limitations of the prior art.
It is a further object of the present invention to provide a chemical sensor that features the benefits of GC and FAIMS but is able to operate rapidly with reduced processing time.
It is a further object of the present invention to provide a chemical sensor that features the benefits of GC and FAIMS but is able to detect multiple species at one time.
It is a further object of the present invention to provide a chemical sensor that features the benefits of GC and FAIMS but is able to generate orthogonal data that fully identifies a detected species.
It is a further object of the present invention to provide a chemical sensor that features the benefits of GC and FAIMS but is able to detect positive and negative ions simultaneously.
It is a further object of the present invention to provide a fieldable chemical sensor that includes both a small ion injector/column and a small detector/spectrometer and yet is able to rapidly produce unambiguous orthogonal data for identification of a variety of chemical compounds in a sample.
It is a further object of the present invention to enable a new class of chemical sensors that can rapidly produce unambiguous, real-time or near real-time, in-situ, orthogonal data for identification of a wide range of chemical compounds.
It is a further object of the present invention to provide sensors that have the ability to detect both positive and negative ions simultaneously and achieving reduction of analysis time.
It is a further object of the present invention to provide a class of sensors that have the ability to use the reactant ion peak to extract the retention time data from a GC sample.
It is a further object of the present invention to provide a class of sensors that have the ability to make 2-D and 3-D displays of species information as obtained.
It is a further object of the present invention to provide a class of sensors that enable use of pattern recognition algorithms to extract species information.
It is a further object of the present invention to provide a class of sensors that do not require consumables for ionization.
It is a further object of the present invention to provide a class of sensors that provide differential-mobility spectra information in addition to the retention time data.
It is a further object of the present invention to provide a class of sensors that can eliminate the need to run standards through the GC.
It is a further object of the present invention to provide a class of sensors utilizing arrays of FAIMS devices each tuned to detect a particular compound, such that multiple compounds can be simultaneously detected rapidly, with simplified electronics.
It is a further object of the present invention to provide a GC detector which detects compounds by ionizing eluted sample and uses different amplitudes of an applied high filed asymmetric waveform to produce different levels of ion clusters, which can be useful in more precise species identification.
It is a further object of the present invention to provide a class of sensors utilizing arrays of FAIMS devices to provide redundancy in ion detected.
It is a further object of the present invention to provide a class of sensors utilizing arrays of FAIMS devices where each ion filter has its own flow path (or flow channel) and is doped with a different dopant for better compound identification.
It is a further object of the present invention to provide a class of sensors utilizing arrays of FAIMS devices each swept over an assigned bias range of the spectrum to obtain faster analysis of the contents of an eluted GC peak.
It is a further object of the present invention to provide a class of detectors that can provide information on the cluster state of ions and ion kinetics by varying the amplitude of the high voltage asymmetric electric field or by adjusting the flow rate of ions through the device.
It is a further object of the present invention to provide a chemical sensor that features the benefits of GC and FAIMS but is able to detect positive and negative ions simultaneously by providing a longitudinal flow path in which positive and negative ions are carried simultaneously through the filter to the detector for simultaneous independent detection.
It is a further object of the present invention to provide a class of sensors that can detect samples over a wide range of concentrations through a controlled dilution of the amount of sample delivered to the PFAIMS through appropriate control of the ratios the amounts of drift, carrier and sample gasses.
It is further an object of this invention to provide a class of sensors that can quantitatively detect samples over a wide range of concentrations through controlled dilution by regulating the amount of ions injected into the ion filter region by controlling the potentials on deflector electrodes.